1. Field of the Invention
The present invention relates to stem cells having a thin multilayer structure, a method of preparing the same, and use thereof for cytotherapy.
2. Discussion of Related Art
Mesenchymal stem cells have the ability to differentiate into various tissue cells, thus attracting attention as a therapeutic material for treatment of immune-related diseases or tissue regeneration. Accordingly, a variety of research into mesenchymal stem cells is actively underway. However, despite such usability, the utilization of mesenchymal stem cells as a therapeutic agent is known to be limited due to intrinsic vulnerability thereof. As an example, a method of simply injecting a single stem cell into the blood is mainly used in treatment of immune-related diseases (A. Tyndall and V. Pistoia, Nature Medicine, 2009, 15, 18). However, upon such single cell injection, the stability of the injected single cell is decreased and it is difficult to deliver the single cell to a target tissue or organ due to various physical, chemical stresses in the blood having high pressure and speed. In addition, when stem cells differentiate into various cells and tissues, the stem cells should be treated in a specific differentiation medium for a long time to induce differentiation thereof, which is an inconvenient process.
To overcome such disadvantages, research into improving the stability and functions of cells by modifying surfaces thereof has been reported. The Ali Khademhosseini group in the U.S. developed a cell culture platform which is stable relative to various chemical stimuli by attaching mouse cardiocytes to gelatin hydrogel and then covering surfaces of the cells with silica hydrogel in a sol-gel manner in order to stably and easily culture cells (C. Cha et al., Biomacromolecules, 2014, 15, 283). In addition, the Akashi group in Japan produced a thin multilayer film using fibronectin, gelatin, which is ECM components, as building materials of an actual ECM in order to stably maintain cells under external physical stress (strong centrifugal force) (A. Matsuzawa et al., Langmuir, 2014, 29, 7362). Further, the Choi group developed stable cells with respect to external enzymes, such as trypsin, by silica-coating HeLa cells (J. Lee et al., Angewante Chemie International Edition, 2014, 53, 8056).
However, conventional technologies relate to cells having relatively high survivability, except for normal stem cells, whereby, when the technologies are applied to stem cells, survivability or functionality thereof may be reduced. In addition, since most conventional cell coating technologies under investigation relate to a technology of coating silica with low penetrability and metal-based materials, various cell-cell interactions are spontaneously deteriorated. Accordingly, application of the technologies to stem cells is not appropriate. In addition, since conventional technologies are performed in an environment different from a real cell culture environment, they are not suitable for stem cell culture.
Therefore, there is a need for a new method of improving the stability of stem cells in an environment similar to a real cell culture environment.